In this western, the Three Mesquiteers must find a killer and his band after they murder an official from the State Agricultural Service who had come to investigate an outbreak of hoof and mouth disease. The killer is fearful that the official would quarantine his entire herd. Unfortunately for the foolish rancher, if the herd is not isolated, all of his cows and those of his neighbors will die anyway. The heroes are assisted by Buck the clever Great Dane.